RGMb-Reduced T Cell Therapy with Checkpoint Blockade
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Solution Overview
Problem
Current T cell therapies are susceptible to immunosuppression and have limited sustained efficacy, and a significant fraction of cancer patients do not respond to immune checkpoint blockade therapies, necessitating new approaches to enhance T cell-based treatments and overcome immunosuppression.
Innovation Solution
Combining T cell therapy with immune checkpoint inhibitors, specifically targeting RGMb expression or activity in T cells, and administering agents that bind to PD-1 or PD-L1 to enhance T cell efficacy and overcome immunosuppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cell therapy is used to treat cancer, then the therapeutic effect is improved, but the T cells become susceptible to immunosuppression and have limited sustained efficacy
Solution Approach 1:
The patent uses immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies) as intermediary substances that block the immunosuppressive pathways. These inhibitors act as mediators between the T cells and the immunosuppressive environment, preventing the harmful interaction while allowing the therapeutic effect to persist.
Solution Approach 2:
The patent modifies the functional parameters of T cells by changing their immunosuppressive state through combination therapy. By altering the immunosuppressive pressure on T cells via immune checkpoint inhibitors, the T cells maintain their therapeutic activity longer, transforming their temporal profile from transient to sustained efficacy.
2Reliability
If immune checkpoint blockade therapy is used, then T cell activation is enhanced, but a significant fraction of cancer patients do not respond to the therapy
Solution Approach 1:
The patent combines immune checkpoint inhibitors with T cell therapy to create a synergistic effect. This merging of two therapeutic approaches addresses the limitation of single-modality therapy by simultaneously blocking immunosuppression and providing direct T cell-mediated cytotoxicity, thereby improving overall response rates across diverse patient populations.
Solution Approach 2:
The treatment approach uses a composite therapeutic strategy combining multiple mechanisms: immune checkpoint inhibitors (antibodies), T cell products (cells), and potentially other adjuvants. This composite approach leverages the complementary strengths of each component to overcome the variability in patient response that limits single-agent efficacy.
3Duration of action of moving object
If first generation T cell therapies are used, then initial treatment effect is achieved, but rapid immunosuppression occurs and sustained effect is limited
Solution Approach 1:
The patent applies preliminary anti-action by pre-treating with immune checkpoint inhibitors before or concurrent with T cell administration. This preemptive blocking of immunosuppressive pathways prevents the rapid immunosuppression that would otherwise occur, thereby extending the duration of T cell therapeutic effect.
Solution Approach 2:
The combination therapy ensures continuity of useful action by maintaining T cell activity throughout the treatment course. The immune checkpoint inhibitors continuously block immunosuppression, allowing T cells to maintain their cytotoxic function without the rapid decline characteristic of first-generation therapies.
Data Source
AI summary
Provided herein are methods and compositions for treating cancer or a tumor in a subject by administering to the subject T cells with reduced RGMb expression or activity and an immune checkpoint inhibitor such as a PD-1 or PD-L1 inhibitor.